Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis

doi:10.1093/nsr/nwab232

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	Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis
	Jin, Yujuan 1,2,3; Zhao, Qiqi 1,2,3; Zhu, Weikang 4; Feng, Yan 1,2,3; Xiao, Tian 5; Zhang, Peng 6; Jiang, Liyan 7; Hou, Yingyong 8; Guo, Chenchen 1,2,3; Huang, Hsinyi 1,2,3; Chen, Yabin 1,2,3; Tong, Xinyuan 1,2,3; Cao, Jiayu 1,2,3; Li, Fei 1,9; Zhu, Xueliang 2,3,10; Qin, Jun 11; Gao, Dong 1,2,3; Liu, Xin-Yuan 1,2,3; Zhang, Hua 12; Chen, Luonan 1,2,3,14; Thomas, Roman K.13,15; Wong, Kwok-Kin 12; Zhang, Lei 1,2,3,14; Wang, Yong4,14 ; Hu, Liang 1,2,3; Ji, Hongbin 1,2,3,14
	2022-07-01
发表期刊	NATIONAL SCIENCE REVIEW
ISSN	2095-5138
卷号	9 期号:7 页码:15
摘要	Small-cell lung cancer (SCLC) is a recalcitrant cancer characterized by high metastasis. However, the exact cell type contributing to metastasis remains elusive. Using a Rb1(L/L)/Trp53(L/L) mouse model, we identify the NCAM(hi)CD44(lo/-) subpopulation as the SCLC metastasizing cell (SMC), which is progressively transitioned from the non-metastasizing NCAM(lo)CD44(hi) cell (non-SMC). Integrative chromatin accessibility and gene expression profiling studies reveal the important role of the SWI/SNF complex, and knockout of its central component, Brg1, significantly inhibits such phenotypic transition and metastasis. Mechanistically, TAZ is silenced by the SWI/SNF complex during SCLC malignant progression, and its knockdown promotes SMC transition and metastasis. Importantly, ectopic TAZ expression reversely drives SMC-to-non-SMC transition and alleviates metastasis. Single-cell RNA-sequencing analyses identify SMC as the dominant subpopulation in human SCLC metastasis, and immunostaining data show a positive correlation between TAZ and patient prognosis. These data uncover high SCLC plasticity and identify TAZ as the key molecular switch in orchestrating SCLC phenotypic transition and metastasis.
关键词	small cell lung cancer SWI SNF complex TAZ phenotypic transition metastasis
DOI	10.1093/nsr/nwab232
收录类别	SCI
语种	英语
资助项目	National Natural Science Foundation of China[81871875] ; National Natural Science Foundation of China[82173340] ; National Natural Science Foundation of China[82030083] ; National Natural Science Foundation of China[81872312] ; National Natural Science Foundation of China[82011540007] ; National Natural Science Foundation of China[31621003] ; National Natural Science Foundation of China[81402371] ; National Natural Science Foundation of China[12025107] ; National Basic Research Program of China[2017YFA0505501] ; National Basic Research Program of China[2020YFA0803300] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB19020201] ; Basic Frontier Scientific Research Program of the Chinese Academy of Sciences[ZDBSLY-SM006] ; International Cooperation Project of the Chinese Academy of Sciences[153D31KYSB20190035] ; Innovative Research Team of High-Level Local Universities in Shanghai[SSMU-ZLCX20180500] ; Science and Technology Commission of Shanghai Municipality[21ZR1470300]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000883232400001
出版者	OXFORD UNIV PRESS
引用统计
文献类型	期刊论文
条目标识符	http://ir.amss.ac.cn/handle/2S8OKBNM/60699
专题	应用数学研究所
通讯作者	Wang, Yong; Hu, Liang; Ji, Hongbin
作者单位	1.Chinese Acad Sci, State Key Lab Cell Biol, Shanghai 200031, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Shanghai 200031, Peoples R China 3.Chinese Acad Sci, Ctr Excellence Mol Cell Sci, Shanghai 200031, Peoples R China 4.Chinese Acad Sci, Key Lab Management Decis & Informat Syst, Natl Ctr Math & Interdisciplinary Sci,Acad Math &, Ctr Excellence Math Sci,Hua Loo Keng Ctr Math Sci, Beijing 100190, Peoples R China 5.Shenzhen Univ, Shenzhen Key Lab Translat Med Tumor, Dept Cell Biol & Genet, Hlth Sci Ctr, Shenzhen 518060, Peoples R China 6.Tongji Univ, Shanghai Pulm Hosp, Shanghai 200092, Peoples R China 7.Shanghai Jiao Tong Univ, Shanghai Chest Hosp, Shanghai 200030, Peoples R China 8.Fudan Univ, Zhongshan Hosp, Shanghai 200032, Peoples R China 9.Fudan Univ, Dept Pathol, Sch Basic Med Sci, Shanghai 200032, Peoples R China 10.Shanghai Tech Univ, Sch Life Sci & Technol, Shanghai 200120, Peoples R China 11.Chinese Acad Sci, CAS Key Lab Tissue Microenvironm & Tumor, CAS Ctr Excellence Mol Cell Sci, Shanghai Inst Nutr & Hlth Sci, Shanghai 200031, Peoples R China 12.New York Univ, Langone Med Ctr, Laura & Isaac Perlmutter Canc Ctr, New York, NY 10016 USA 13.Univ Cologne, Dept Translat Gen, Ctr Integrated Oncol, D-50931 Cologne, Germany 14.Univ Chinese Acad Sci, Sch Life Sci, Hangzhou Inst Adv Study, Hangzhou 310024, Peoples R China 15.Univ Hosp Cologne, Dept Pathol, D-50937 Cologne, Germany
推荐引用方式 GB/T 7714	Jin, Yujuan,Zhao, Qiqi,Zhu, Weikang,et al. Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis[J]. NATIONAL SCIENCE REVIEW,2022,9(7):15.
APA	Jin, Yujuan.,Zhao, Qiqi.,Zhu, Weikang.,Feng, Yan.,Xiao, Tian.,...&Ji, Hongbin.(2022).Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis.NATIONAL SCIENCE REVIEW,9(7),15.
MLA	Jin, Yujuan,et al."Identification of TAZ as the essential molecular switch in orchestrating SCLC phenotypic transition and metastasis".NATIONAL SCIENCE REVIEW 9.7(2022):15.